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Induction chemotherapy, extrapleural pneumonectomy (EPP), and adjuvant hemithoracic radiation are feasible and effective for locally advanced malignant pleural mesothelioma (MPM).

SOURCE: ASCO, 2004 Annual Meeting

R. M. Flores, L. Krug, K. E. Rosenzweig, A. Vincent, T. Akhurst, R. Heelan, V. W. Rusch; Memorial Sloan-Kettering Cancer Center, New York, NY

Background: Approximately 25% of patients (pts) with malignant pleural mesothelioma (MPM) prove unresectable at surgery and the median survival of stage III MPM is <12 months even after complete resection by extrapleural pneumonectomy (EPP). Improving chemotherapy for MPM led us to test induction chemotherapy followed by EPP and adjuvant hemithoracic radiation (RT) for locally advanced MPM to assess feasibility and estimate survival.

Methods: From 1/2002 - 12/2003, pts with T3-4 or N2 MPM by CT and PET scans were enrolled on a phase II study. Induction therapy was: gemcitabine (1250mg/m2days 1, 8) and cisplatin (75mg/m2 day 8) x 2-4 cycles. Pts underwent EPP 3-5 weeks after induction therapy, then 54 Gy RT 4-6 weeks postop. CT scans were followed every 3 months thereafter. Chemotherapy response was assessed by RECIST criteria. Overall survival was assessed by Kaplan-Meier.

Results: 21 pts (15 men, median age = 60 years) were consented to study, 19 received chemotherapy. MPM histology was epithelial = 14, mixed or sarcomatoid =5. 10 pts completed 4 chemotherapy cycles, while 9 received 1-2 cycles. No grade 4 toxicities occured. Chemotherapeutic responses were: complete = 0, partial = 5 (26%), stable =11 (58%), progression = 3 (16%). At surgery, 8/9 pts had complete resection by EPP with no postop deaths. All of these pts received planned adjuvant RT. By Kaplan-Meier, pts undergoing EPP had a 75% survival at 18 months (median follow-up = 8 months), while no pts were alive at 18 months without surgery (log rank p=0.03).

Conclusions: This combined modality approach is feasible for locally advanced MPM, and initial analysis suggests a favorable survival for pts rendered resectable. This experience supports additional studies of induction and multimodality therapy, especially with regimens such as cisplatin and pemtrexed which may be better tolerated and more effective.